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Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases
Different alterations of cytochrome P450 3A4 isoform and its gene expression in livers of patients with chronic liver diseases
- Source :
- World Journal of Gastroenterology. 9:359
- Publication Year :
- 2003
- Publisher :
- Baishideng Publishing Group Inc., 2003.
-
Abstract
- AIM: To determine whether parenchymal cells or hepatic cytochrome P450 protein was changed in chronic liver diseases, and to compare the difference of CYP3A4 enzyme and its gene expression between patients with hepatic cirrhosis and obstructive jaundice, and to investigate the pharmacologic significance behind this difference. METHODS: Liver samples were obtained from patients undergoing hepatic surgery with hepatic cirrhosis (n = 6) and obstructive jaundice (n = 6) and hepatic angeioma (controls, n = 6). CYP3A4 activity and protein were determined by Nash and western bloting using specific polychonal antibody, respectively. Total hepatic RNA was extracted and CYP3A4cDNA probe was prepared according the method of random primer marking, and difference of cyp3a4 expression was compared among those patients by Northern blotting. RESULTS: Compared to control group, the CYP3A4 activity and protein in liver tissue among patients with cirrhosis were evidently reduced. (P < 0.01) Northern blot showed the same change in its mRNA levels. In contrast, the isoenzyme and its gene expression were not changed among patients with obstructive jaundice. CONCLUSION: Hepatic levels of P450s and its CYP3A4 isoform activity were selectively changed in different chronic liver diseases. CYP3A4 isoenzyme and its activity declined among patients with hepatic cirrhosis as expression of cyp3a4 gene was significantly reduced. Liver's ability to eliminate many clinical therateutic drug substrates would decline consequently, These findings may have practical implications for the use of drugs in patients with cirrhosis and emphasize the need to understand the metabolic fate of therapeutic compounds. Elucidation of the reasons for these different changes in hepatic CYP3A4 may provide insight into more fundamental aspects and mechanisms of imparied liver function.
- Subjects :
- Adult
Male
Gene isoform
medicine.medical_specialty
Cirrhosis
Gene Expression
Biology
Isozyme
Cytochrome P-450 Enzyme System
Clinical Research
Internal medicine
Gene expression
medicine
Cytochrome P-450 CYP3A
Humans
Protein Isoforms
Northern blot
CYP3A4
medicine.diagnostic_test
Liver Diseases
Gastroenterology
General Medicine
Middle Aged
medicine.disease
Endocrinology
Liver
Chronic Disease
Female
Liver function
Liver function tests
Subjects
Details
- ISSN :
- 10079327
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- World Journal of Gastroenterology
- Accession number :
- edsair.doi.dedup.....35c7db1e8c654ca4c80494674b1c5ab0
- Full Text :
- https://doi.org/10.3748/wjg.v9.i2.359